Dopamine D2 and D3 Receptor Occupancy and Clinical Response in Older Patients With Schizophrenia

• Status: Active, not recruiting
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will provide information regarding dopamine D2/D3 occupancy related with clinical/adverse effects in older people with schizophrenia and schizoaffective disorder. The results of this study will also show an appropriate dose range in order to evade undesirable adverse effects while deriving therapeutic effects, which will directly serve to guide physicians in clinical practice. Furthermore, the findings of this study will elucidate mechanisms underlying older people's increased sensitivity to antipsychotic drugs. In addition, the contribution of D2 and D3 in mediating antipsychotic response will be contrasted, using 2 radiotracers, which has never been tested in an older population.

The hypotheses are as follows: First, clinical response (i.e., a ≥ 20% decrease in the Brief Psychiatric Rating Scale total score) will be achieved in older patients with occupancy that is lower than the threshold of 60% in historical young controls. Second, prolactin elevation and EPS will be detected in older patients with occupancies that are lower than the thresholds of 72 and 78% reported in historical young controls. Third, dopamine D2 receptor occupancy will be inversely correlated with subjective well-beings. Fourth, the binding potential and receptor occupancy will be at least 20% lower with [11C]-(+)-PHNO than with [11C]-raclopride in the caudate/putamen. Fifth, the binding of [11C]-(+)-PHNO in the globus pallidus will be higher than that of [11C]-raclopride.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre for Addiction and Mental Health
• Treatments: Dopamine; Dopamine Agents; Risperidone

Criteria

Inclusion Criteria:

• Age of 50 and older at time of scanning

• Inpatients or outpatients

• DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder

• Having NOT been treated with oral antipsychotic treatment for at least 2 weeks or long-acting antipsychotics for at least 6 months (Please note that patients will not be withdrawn from antipsychotic medications for the purpose of meeting inclusion criteria for this study).

Exclusion Criteria:

• Known history of intolerance or inefficacy to risperidone

• Participation in this study would result in exceeding the annual radiation dose limits (20 mSv) for human subjects participating in research studies.

• Substance abuse or dependence (within past six months)

• Positive urine drug screen

• Positive serum pregnancy test at screening or positive urine pregnancy test before PET scan

• Metal implants or a pace-maker that would preclude the MRI scan

• History of head trauma resulting in loss of consciousness >30 minutes that required medical attention

• Unstable physical illness or significant neurological disorder including a seizure disorder

• Inappropriate size of head, neck, and body to be able to fit the PET and MRI scans